Journal article
Conformational States Control Lck Switching between Free and Confined Diffusion Modes in T Cells.
- Hilzenrat G EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia; Commonwealth Scientific and Industry Research Organization (CSIRO), Manufacturing, Clayton, Victoria, Australia.
- Pandžić E BioMedical Imaging Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia.
- Yang Z EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia.
- Nieves DJ EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia; Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
- Goyette J EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia.
- Rossy J Biotechnology Institute Thurgau, University of Konstanz, Kreuzlingen, Switzerland.
- Ma Y EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia.
- Gaus K EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia. Electronic address: k.gaus@unsw.edu.au.
- 2020-02-26
Published in:
- Biophysical journal. - 2020
English
T cell receptor phosphorylation by Lck is an essential step in T cell activation. It is known that the conformational states of Lck control enzymatic activity; however, the underlying principles of how Lck finds its substrate over the plasma membrane remain elusive. Here, single-particle tracking is paired with photoactivatable localization microscopy to observe the diffusive modes of Lck in the plasma membrane. Individual Lck molecules switched between free and confined diffusion in both resting and stimulated T cells. Lck mutants locked in the open conformation were more confined than Lck mutants in the closed conformation. Further confinement of kinase-dead versions of Lck suggests that Lck confinement was not caused by phosphorylated substrates. Our data support a model in which confined diffusion of open Lck results in high local phosphorylation rates, and inactive, closed Lck diffuses freely to enable long-range distribution over the plasma membrane.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1016/j.bpj.2020.01.041
- PMID 32097620
- Persistent URL
- https://sonar.ch/global/documents/279143
Statistics
Document views: 14
File downloads: